title: Luteinizing hormone (LH) acts through PKA and PKC to modulate T-type calcium currents and intracellular calcium transients in mice Leydig cells.
abstract: LH increases the intracellular Ca(2+) concentration ([Ca(2+)](i)) in mice Leydig cells, in a process triggered by calcium influx through T-type Ca(2+) channels. Here we show that LH modulates both T-type Ca(2+) currents and [Ca(2+)](i) transients through the effects of PKA and PKC. LH increases the peak calcium current (at -20mV) by 40%. A similar effect is seen with PMA. The effect of LH is completely blocked by the PKA inhibitors H89 and a synthetic inhibitory peptide (IP-20), but only partially by chelerythrine (PKC inhibitor). LH and the blockers induced only minor changes in the voltage dependence of activation, inactivation or deactivation of the currents. Staurosporine (blocker of PKA and PKC) impaired the [Ca(2+)](i) changes induced by LH. A similar effect was seen with H89. Although PMA slowly increased the [Ca(2+)](i) the subsequent addition of LH still triggered the typical transients in [Ca(2+)](i). Chelerythrine also does not avoid the Ca(2+) transients, showing that blockage of PKC is not sufficient to inhibit the LH induced [Ca(2+)](i) rise. In summary, these two kinases are not only directly involved in promoting testosterone synthesis but also act on the overall calcium dynamics in Leydig cells, mostly through the activation of PKA by LH.
authors.affiliation: Department of Physiology, School of Medicine of Ribeirão Preto/University of São Paulo, Av. Bandeirantes, 3900, 14049-900 Ribeirão Preto, SP, Brazil.
authors.forename: Roberta Ribeiro
authors.initials: RR
authors.lastname: Costa
authors.forename: Rosana Inácio Dos
authors.initials: RI
authors.lastname: Reis
authors.forename: José Fernando
authors.initials: JF
authors.lastname: Aguiar
authors.forename: Wamberto Antonio
authors.initials: WA
authors.lastname: Varanda
mesh_terms: D000818:Animals; D053119:Benzophenanthridines / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D020747:Calcium Channels, T-Type / Q000737:chemistry / Q000378:metabolism*; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D055724:Electrophysiological Phenomena; D007546:Isoquinolines / Q000494:pharmacology; D007985:Leydig Cells / Q000378:metabolism*; D007986:Luteinizing Hormone / Q000494:pharmacology*; D008297:Male; D051379:Mice; D010455:Peptides / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019311:Staurosporine / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D053119:Benzophenanthridines; D020747:Calcium Channels, T-Type; D007546:Isoquinolines; D010455:Peptides; D013449:Sulfonamides; C016658:phorbolol myristate acetate; D007986:Luteinizing Hormone; C058824:IP 20; C016299:chelerythrine; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D019311:Staurosporine; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium